1. Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage.
- Author
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Roda RH, Rinaldi C, Singh R, Schindler AB, and Blackstone C
- Subjects
- Apraxias congenital, Brain pathology, Cell Nucleus metabolism, Cells, Cultured, Cerebellar Ataxia genetics, Cerebellar Ataxia pathology, Cogan Syndrome genetics, Cogan Syndrome pathology, Colombia, DNA Helicases, Female, Forearm physiopathology, Frameshift Mutation, Humans, Middle Aged, Multifunctional Enzymes, Mutation, Missense, Pedigree, Phenotype, RNA Helicases genetics, RNA Helicases metabolism, Cerebellar Ataxia physiopathology, Cogan Syndrome physiopathology, DNA Damage physiology, Fibroblasts physiology, Oxidative Stress physiology
- Abstract
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive cerebellar ataxia associated with mutations in SETX, which encodes the senataxin protein, a DNA/RNA helicase. We describe the clinical phenotype and molecular characterization of a Colombian AOA2 patient who is compound heterozygous for a c.994 C>T (p.R332W) missense mutation in exon 7 and a c.6848_6851delCAGA (p.T2283KfsX32) frameshift deletion in SETX exon 21. Immunocytochemistry of patient-derived fibroblasts revealed a normal cellular distribution of the senataxin protein, suggesting that these mutations do not lead to loss or mis-localization of the protein, but rather that aberrant function of senataxin underlies the disease pathogenesis. Furthermore, we used the alkaline comet assay to demonstrate that patient-derived fibroblast cells exhibit an increased susceptibility to oxidative DNA damage. This assay provides a novel and additional means to establish pathogenicity of SETX mutations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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